Transcript of an interview with Aaron Ciechanover

Aaron Ciechanover during the interview

Aaron Ciechanover during the interview.

Transcript from an interview with Aaron Ciechanover, 2004 Nobel Laureate in Chemistry, at the 57th Meeting of Nobel Laureates in Lindau, Germany, July 2007. The interviewer is Adam Smith, Editor-in-Chief of

Aaron Ciechanover, co-recipient with Avram Hershko and Irwin Rose of the 2004 Nobel Prize in Chemistry, welcome to this interview. I’d like to start by just exploring a few general themes. When I say the word mentorship, what does that conjure up?

Aaron Ciechanover: For me it was very important in particular because in my case at least I shared the prize with my own supervisor. And so it means a lot. I was lucky to have an excellent mentor. I don’t know if the word luck is proper here because I picked him by purpose, not because I knew that one day both of us were going to share the Nobel Prize, but I really searched around. And I had the privilege of searching around because I was a physician already, a practising physician and I had my own career, basically paved, or at least I could see where I was heading. But then I decided to change direction and to go to research. I did it already in medical school but then I went back to medicine and I kind of flipped back and forth, back and forth. And I hadn’t made my mind yet.

And then I decided never the less to try science  …

And then I decided never the less to try science and I went around and explored the possibilities with several potential mentors. And each of them was very clear about his ideas. Let’s do that and let’s do that, and I did that and you know whatever is left here. And Avram was a young investigator, just came back from a post doctoral fellowship, I mean he himself … And there he started to work on protein degradation, basically just corroborated previous findings from the past, some paradoxical findings that protein degradation requires metabolic energy, typically it’s the opposite. When you synthesise proteins you need energy. Why invest energy if you are taking high energy compounds and degrade them into low energy ingredients, which are amino acids? And Avram told me: I don’t know what I am going to do. All I know that I want to identify the system that degrades into solo proteins. I don’t know how to do it, I don’t know where it is, I don’t know how it’s going to look like.

So he had some ideas and for me I said: Wow, that’s wonderful, this risky way. And he said: Let’s take it for two or three years and see, you know, if we are going to bump to the wall, I’ll go back to the OR, to the operations theatre. I had in my mind to be a surgeon. And if I get excited, even if we don’t get results, I mean if I get excited about it I’ll stay. And it was wonderful. Avram is an excellent biochemist, and after a short time we realised that we had something very unusual at hand. And then it continued. I learnt a lot from him. But you know it was kind of a dialogue, an active dialogue. I thought that good mentors, I don’t want to be proud, they need also maybe good students. Certain interaction. But Avram certainly had the idea to work on the system, though he didn’t know what’s behind the corner.

So mentorship is partly sort of colleagues seeking the same goal and being open to discussion.

Aaron Ciechanover: You know, you have to know when to trust your mentor, whether to find him blindly, when to challenge him, when to do something on your own like use the nights or the weekends when he is not there. And if you fail, don’t tell him that you have ever been to the lab. If you are successful tell him: Hey, I told you. So it’s kind of dynamic interaction that you have to find your own way. And then obviously there is the post doctoral fellowship when you further evolve and you need another mentor and it’s critical. It’s really critical.

And do you think you provide good mentorship for your students? Do you follow those principles?

Aaron Ciechanover: I hope so, I hope so. I am different. You know, we are different people. I think that Avram was a little bit more tight, but that’s okay, I mean that’s his nature. I give them freedom, so I let them drown. I learnt more from my American mentor about mentorship than from him. I let them drown and if they feel that they have taken too much water into the lungs then they know that my door is always open. And so I never turn them down but I want them to evolve you know more independent.

But it’s a matter of taste, of how you go about them. I don’t let them die by drowning, I just let them drown. And I give them all freedom. But it’s a matter of personal style. I encourage them to, I never turn them down by telling them: Oh, you know, you shouldn’t have done it. I always let them do mistakes. But then we analyse the mistakes. I refer them to the literature in the entire lab. Whenever I read something, I refer them to the literature. Many journal’s club, you know, what’s the mistakes? It’s not just reporting on the journal. So it’s maybe a little bit different mentorship but I take, I think, don’t know if good, whether it’s good or bad, you have to ask them, but at least intensive care.

And critical reading of the literature?

Aaron Ciechanover: And critical reading and critical evaluation of their own results. And they have to write their own papers. For example, I didn’t write my own papers. Avram wrote them, wrote them mostly. I let them write and then we’ll discuss, you know. We read them together and obviously I have the final touch. But, you know, we said: No this figure should be first because this is really the one that was the important and led us into this. And we develop it by logic, figure one, figure two, so we make a story, we make an alphabet out of the paper. And then the discussion. I put a lot of emphasis on the discussion. How did we think about it? What’s, what we still have to find out?

… mentorship is extremely important …

So it’s kind of a more dynamic, of a very dynamic interaction. I feel it a little bit more dynamic than I had with Avram but I think that it’s a matter of taste. I mean it’s not something principle. Altogether I was extremely lucky to have two excellent mentors. One is Avram, with him we found the system. And another one is Harvey Lodish at MIT with whom I post doc-ed. And he gave me, he is a mentor of my own style. I mean he said: Do that but he didn’t go into the details. But then when I came to him with a problem he knew always how to, you know, when he felt that I am derailed he was able to just put me back on by a slight tap on my shoulder and not a push. Just a hint of what to do. And I think that I adapted more his style. But never the less, mentorship is extremely important.

When you come to choose a student what do you look for in the student?

Aaron Ciechanover: First of all I want him to have the background of what I do. I don’t want students to knock on my door and to say whether I have a spot. So the first question that I ask them is: Why me, why not my next door neighbour or my next floor neighbour or whatever. Why me? And then he said: Well, I read about you. I said what did you read? And then he comes and he tells me what did he read. And then I said: What do you think, what shall we do? I mean are there still open questions? I’m not asking them to give me, to come right there with a project. I want to identify the structure motif in the Myc onco protein. I mean we are not going to there. But what do you think about it? And somehow from time to time they’re very naïve about it. I mean they want to develop drugs, but I take it in their proper context. I mean I don’t take this naivety against them. As long as I’m convinced that they’ve read, they know why they picked me, they know the problems in the field, what is still there.

And then I never take a student, I never promise them studentship. I say I take you for a trial. Start work, I’ll pay you, as a technician, super technician, for three or four months. And then I assign them to another student or a post doc, and then I follow them myself, and with them I really carry out a very extensive dialogue along these three months. And then at the end of the three months all the group consults together about first and foremost about the scientific skills. Then also about social skills. We want the lab to be not homogenous but we want people to be good departmental citizens, you know. I very much care about the good atmosphere in the lab. And then we don’t vote but I get the sense and I myself know the candidate and so it’s a process.

It’s a great idea. And you’ve also had an investment of faith from the student.

Aaron Ciechanover: Exactly. And they feel that it also gives to the students a feeling that they are, that one day I’m not parachuting on their heads. Somebody can tell them, well, he will be your next bench neighbour. They are part of the lab and they care about it and they understand why, because they really by themselves they want to keep the good atmosphere in the lab. So that’s also an important factor. And we deal with it. We sit for an hour during group meetings, you know, one of our weekly group meetings and then we’ll say now we have to first discuss Mr X or Mrs Y and we do it together. And somebody says: No, he is not organised, he leaves mess behind. I say is this a good reason just to tell him not to come or can we tell him directly, you have to be considerate of other people? And then we all agree.

Nice and open. Talking of the atmosphere …

Aaron Ciechanover: The students are my partners in many ways. The students and the fellows, my lab and my research associates, they are not just working for me.

Talking of the atmosphere in the lab, what kind of environment do you encourage? How physically do you organise the lab?

Aaron Ciechanover: Oh the lab is, first of all it’s very well equipped. We are very sophisticated. We have everything that we need almost on the floor, except obviously for proteomics and mass spectrometers. We have all the microscopes and everything that we need, time lapse, fluorescence, ConfoCor, whatever we need we have. And so the lab is very well equipped. My two research associates take care of everything. Cleanliness, orders, badgets, everything, so that’s beyond me. But we’re organised in clusters. So we are working, we are about 15 or 14 people and we are working about three or four projects. So three or four students, typically one post doc and two or three students are working on the same project. But it’s the same by title. They don’t compete against one another. I hate it. They study different aspects of the same problem.

Is it common that people do get their students to compete over the same project do you think?

Aaron Ciechanover: I heard so. I don’t want to comment. But yes I know so. But again I’m not, it’s for me inhumane in the worst sense of the word. So for example now we are studying polycomb complexes, repressive complexes, and they have many components. So one studies one component, the other studies one, and then they can talk to one another and then they share probs. And since the lab is entirely ubiquitin lab, so even between the clusters they can share in the group because everybody understands the language. So one group is working on meek degradation, another group is working on NF-KB, another group is working on polycomb, another group is working on apoptosis. So basically that’s it. Now we have four clusters, about three to four in each. And so it’s mostly kind of collaboration. Collaborative efforts but never the less very distinct individual projects.

And are there are any tricks you use in the way you organise the space to get them to collaborate more than they would otherwise?

Aaron Ciechanover: They are in bays. I mean the lab is very spacious. We designed it. You know it was an empty floor and we designed it to our needs. We were working against the architects for a year and a half and it’s a very unique lab.

Not with them.

… I’m there and my door is always open when I’m there …

Aaron Ciechanover: I was lucky to get some beautiful stipend from the Wolfson Foundation in London and they supported us very generously and I had the privilege to build my own palace. And my room, my office is in the middle of the lab, it’s implanted in the middle so that it’s accessible from all sides. People don’t have to run, I’m not at the end of the corridor. So I’m there and my door is always open when I’m there and so it’s very nice. When I cross the lab, when I come to the office I cross the lab and wherever I walk from my room I cross the lab.

That’s a lovely design. But you say you worked against the architect, not with the architect, but against the architect for a year and a half.

Aaron Ciechanover: In a way we worked, not against him, we worked with him and we gradually evolved an idea and then during the construction we had a little bit change, we moved things and so on and so forth. And we consulted on every – and again my research associates, even the students, took part in it. So how the benches will be, what material. Should it be wood covered with Formica or should it be Trespa, should it be Corian or should it be – and the colours were chosen by all of us. Now we installed music system so there is kind of soothing music all the time in the background.


Aaron Ciechanover: Yes. It’s very helpful, and they do it, the students do it and they choose. When I go to Thailand I buy a whole collection of CDs and then we put it on. And then we have annual retreats also, away from the lab.

Right. So the sound of your lab is music against which there’s a hubbub of conversation.

Aaron Ciechanover: The typical music will be this soothing relaxing music. But if they want to listen, I don’t know, to the Rolling Stones or the Bills or whatever, I mean they can do whatever they want. And if the noise disturbs me I just shut the door. I never tell them to do anything about it.

That’s wonderful. How many people are there in the lab in total?

Aaron Ciechanover: About 15, we are between 12 and 15 all the time. I keep it this size. I don’t want to go higher because then I lose control, I don’t know what they do and in group meetings I really want to know what they are doing. And don’t go much lower than ten because then we lose projects. It happens, you know, it fluctuates, but it’s about that number all the time.

That was fascinating. Thank you. If we turn to your own scientific beginnings, in your Nobel autobiography you write very elegantly and at considerable length about where you came from as a scientist. And you describe that section as falling in love with biology. What was the beginning of the love affair? What got you going?

Aaron Ciechanover: Almost from day one it’s like, but at that time obviously you remember or you know, it was very different biology you know. So I grew up in a city that is in the mountains and much of the city wasn’t settled and the mountain was just open and wild. And I asked my brother. So initially it was simple taxonomy. I collected flowers and dried them out. I think that I wrote in my biography that I dried them out in the Jewish scholarly books, in the Jewish Talmud of my brother, and then he exploded and he got a fit. You know, I took the holiness of the holiness of the Jewish faith and smashed flowers.

It could be worse.

Aaron Ciechanover: It could be worse, yes. So it was mostly defining plants and flowers, to which family they belong, collecting reptiles and so on and so forth. And from the very beginning I always went into biology. So in high school I went to biology and so on.

… by the age of nine I had already my first microscope. And I did experiments …

My brother, he is much older than I am, I have one brother, he is here by the way. And when he went to England I was seven or eight years old, he went to the UK on a mission. Obviously he asked me what do you want, and I wanted one thing, my first microscope. So I think that by the age of nine I had already my first microscope. And I did experiments. I mean I looked into onion cells and I did experiments with osmosis. So I took these onion cells, you know the thin layer of epithelium, and then I soaked it in high salt and I saw it shrink and then I soaked it in water and I saw it blow.

That’s a nice experiment. Where did you get the idea from?

Aaron Ciechanover: I got it from books and I read about it and then I pinched my finger and took blood and smeared it over a cover glass. So I just was looking, I was curious, there was no DNA at that time, nothing. I directed myself. But then I didn’t know what’s biology really, even in high school. And then I had to go to the army and then I said Well I don’t know about science. And the army gave us opportunity, the Israeli army, to go and study first and then serve in the Israeli army in our profession. But you couldn’t go to biology because they were not interested in biologists. They were interested in physicians.

So the army …

Aaron Ciechanover: So I went to medicine and it was very difficult at that time to be accepted. We had only one medical school and I started medicine. But then again I started to feel restless.

I wanted to ask you about because there was just one medical school at that point that was Hebrew.

Aaron Ciechanover: The Hebrew University in Jerusalem, I was accepted and I went to medicine. But then again three or four years into medical studies I became restless again and bored and I said No, I need some fresh air.

Was it strange studying in a medical school that was the only medical school in Israel at the time?

Aaron Ciechanover: Israel was at that time a small country of three or four million people. So that’s what we had. Now we have four. And I became restless again and then I decided to take fresh air for one year and I went to do my master’s degree in science. But then I decided never the less to finish because I still have to serve in the army. And it was like flip flopping for a long time. So I finished, I did my master’s degree in biochemistry, fell in love with biochemistry but then went to complete my medical studies.

And then I had to return my service to serve in the Israeli army. I was a combat physician for three years. And then I still didn’t know so I started surgery. I had a short stint in surgery but then I gave up. I said No, I cannot take care of patients and do the same. And then Avram just came back from his post doc fellowship and I was his second, well, we started together, graduate students. I mean I started immediately with a young post-doctoral fellow that just came back and started his own lab.

Because you’d seen Avram before you went to the military and you worked for him?

Aaron Ciechanover: I knew about him from the medical school. He also graduated. Actually we have followed the same very identical curric ten years apart. Avram is exactly ten years older than I am. He did the same, took one year during the medical studies, finished his medical studies, went to the army, went to do his PhD, went to a post doc. I did the same identical ten years later. It’s like bang, bang, bang, bang, bang. Not that I, only in retrospect when I analysed it I realised that we really followed identical currics. And then I started my PhD and that was the end of clinical medicine.

I mean these days it’s very unusual for people to take three years out to go to the army before doing a PhD. So it would be interesting to know what that gave you. Did it improve?

Aaron Ciechanover: The army gives one I think, it’s a difficult service but I don’t know if it improves you, but it matures you. You take things in proportion, especially that this was the ’73 war, 1973. I served in the army between ’73 and ’76. I started my military service with the Day of Atonement War and fights and wounded and so on and so forth. So it matures you. And then you learn to live with other people of different educational levels because they just came from destroyed homes. It’s an excellent melting pot.

You know, with the khaki uniform you don’t know who is the man behind unless you know him. And then you get to know him and the people are just wonderful. You know, people that hardly can write or read they all of a sudden became your brothers and you would cook together and it’s very pressed. I was in a missile boat, I was a physician on an Israeli missile boat, and it’s crowded, it’s the hot bed system, you don’t have your own bed. Well, I had because I was an officer but, and then you learn, you don’t want to be above them, you want to be with them. So I took a short course and I was standing near the steering wheel of the …, and I was broadcasting the news that came from the shore every day and I became their friend. And then they cook … I mean it’s like, it’s a wonderful melting pot. It matured me. I wouldn’t have given it up. Also nation wise, you’re entering exam into the nation, it’s something, wonderful experience.

I can see that. As you say it must have changed the way you viewed people and data and everything.

Aaron Ciechanover: Completely. I would say that the military service was one of my richest human experiences, if not the richest. Just unbelievable experience.

And students coming into your lab now have in general also done military service?

Aaron Ciechanover: Except to the Israeli Arabs. They don’t serve in the military. And I take a lot of Arabs into my lab because I think education, research science is also an important platform for peace, for attenuating religious extremism. And so there are always some Arab Muslim students in my lab. Currently I have two.

Right. But you see in some ways the same benefits of having people coming in to your lab from the military?

Aaron Ciechanover: Yes, yes, absolutely, absolutely.

Okay, so then you found yourself doing a PhD with Avram and you had this extraordinarily productive and wonderful time when you were sorting out the ubiquitin mediated degradation system. And you were working on a system that was really not that usual to work on. There weren’t that many people trying to explore this.

… this is kind of baloney in a way. What’s important that nobody’s working on?

Aaron Ciechanover: Yes. Avram noted it this morning in his talk and I am going to repeat it tomorrow in my own talk. Quite frankly, you know it’s a wisdom after the deed. I mean when people, Avram tells everybody and I try to tell, but you know, what is your advice to a young scientist in a small country? Work on something important that nobody else is working on. I meant this is kind of baloney in a way. What’s important that nobody’s working on? I mean people are not stupid. I mean there are so many smart people around. If it’s important they work on it. And if it’s not important then why work on it anyway? So I don’t think that it’s a practical advice. But true.

Most people at that time were working on how the genome generates the proton. How the genome is translated into the proton along the famous paradigm DNA RNA protein, we’re splicing, Phil Sharp and Richard Roberts were already there. And Avram was interested in protein degradation which truly was not interesting because there were some hints about it but it’s a fashion in science. And maybe Avram is right, they cannot go back into his reasoning why to choose it. I’m not sure that it was that nobody is working on it. It’s never the less important. He chose it because he felt probably that it was very important to do it and he did it. But it’s true that very few worked on it seriously, very few worked on it seriously, and in retrospect it turned out to be an absolute right strategy. Not because of the Nobel Prize obviously but because of the ubiquitin system that became the discovery itself, that it’s so important basic biological platform on which so many cellular proteolysis are riding. And then pathologists of diseases, drug development, it’s a whole world now.

Given that he was still working out what he was trying to do, presumably his decision to move into this field was partly based on the fact that you’d come to work with him as well.

Aaron Ciechanover: No, no, no. No, no. I should give him the whole credit. He started it on his own as a post doc and there during his post doc with Gordon Tompkins in California he decided to work on it and there he corroborated this strange feature that was discovered initially by Simpson and others in the mid-fifties. That proton degradation requires energy. He had no clue about the mechanism. He was determined that this would be his future project. When I joined him obviously there was nothing known about ubiquitin or anything.

But I liked the risky way that he offered me. He said Let’s start to explore the jungle, whatever is there, and I said Fine. I mean why work on something that somebody left in the lab yesterday and I shall be just another brick in an awfully clear construction road. Let’s just start from scratch and I liked the approach and I chose him. But, no, Avram was the one that had the idea to work on protein degradation though he had no clue what’s ahead of him. So the experiments we started almost from scratch.

Right. And then as you went along and you came up with key findings such as the fact that there wasn’t a single protease, you were dealing with more than one. And then you …

Aaron Ciechanover: This was the one key experiment that we did that told us that we are out of paradigm. I mean it was … within the first year we knew that we are in the jungle completely, we have no, you looked around and nobody can help you. I mean you are out of paradigm.

And when you got to that point there was no question in your mind that you were going to continue.

Aaron Ciechanover: Yes, yes, I said that’s so challenging. And once we discovered the conjugation we knew that it’s so new.

That there was covalent attachments …

Aaron Ciechanover: Covalent attachments to the ubiquitin to the substrate as a proteolysis signal. Then we knew, Wow, big wow. We didn’t know how big is the wow. I mean as far as its importance, but we know it’s a big one as far as its novelty in biology. So we didn’t know the diseases behind the complexity, there was no human genome at that time to tell us that the ubiquitin system consists, is 7-8% of the total human genomes, all the enzymes of the ubiquitin system. We had no clue at that time but we said Wow, biochemically that’s so novel, so away that. And I decided … and it had huge effects on my post-doctoral fellowship as well because I did a very unique and unusual post-doctoral fellowship. So then I knew I’m … that’s my life.

Coming to that in a second. As you were working through these discoveries which would take you further and further away from the known universe so to speak, were you not worried that other people, bigger labs, would pick up on what you were publishing and just take it away faster than you could keep up?

Aaron Ciechanover: You always worry about competition. And there we saw, actually without mentioning names because they are good friends now, we saw them failing around us. Actually we were not the first, if we really probe the history into the date and publication, we were not the first to find the in vitro proteolytic system. Obviously we were the first to fractionate it. There was another good friend, one very famous university in the United States, probably number one university in the United States, huge, starts with H. And he was on, and we were a little bit concerned. But then the beauty of it is, I think, again it’s, you know, we have to be very careful. It’s a retrospective, retroactive analysis.

You cannot, it’s like saying Okay, work on something important that nobody works. I mean this is kind of this type of definition that are non-existing in my mind. But when I analyse it retrospectively why did he fail and he is a good guy, very good guy, I think that he was a proteolysis guy. We worked in parallel. We didn’t take anything from him, absolutely. We were our own. But he was faster or whatever and he published the reticulocytelysate system that we were working on and he was the first to come out. And then he was, we were on the starting line, actually he was ahead of us on the starting line, because he was more … But I think that he was captured with emotion and that tells you how, you cannot be prejudiced and maybe our background … Fred was a proteolysis guy for decades. That’s what he did for life. And I think that he was occupied with a notion that for that this marriage you need only two for this tango. You need a protease and a subscript. He knew that it’s ATP-dependent. But the idea /- – -/ substrate, chymotrypsin substrate.

There were no real serious competitors at that time …

And he said Well I have something which is ATP-dependent, so it’s some crazy protein, it’s unlike trypsin and chymotrypsin. But never the less it’s still the same door to the tango idea. And whenever he put his protease or extract on a column and fractionated it by whatever method, he lost it because the ubiquitin going this way, he went this way, the protease went this way. And he thought Well I lose it because it’s such a gentle complex or maybe I wrap it up with DTT. And DTT was not sufficient and wrap it up with glycerol and this and that. And while he was wrapping up his gentle elusive protease we were fractionating it. And I think the reason, and then we opened the gap of two to three years that he could never close any more. We came out, we poured papers to the literature at a pace of one every two months or every three months. So he just couldn’t keep. And he didn’t believe us as a matter of fact, which was good. He was the only serious contender or competitor at that time. And all the rest, Bob Shimki, they left the field. There were no real serious competitors at that time.

And I think that our luck compared to his was not, you can say we were better, I don’t know, I don’t like this, I don’t compare myself to anybody. I think that we were not preoccupied with any idea because we were not proteolysis people. We were in awe to the field. We never proteolysed the problem, we were never preoccupied with any idea about the system. We lost activity we said well maybe we split it into two, let’s take the two parts, put it together, wow, it worked. And then we took each factor and we took the other one and we further fractionated it and then we skin it again. It was like a puzzle. And at the time that I left the lab there were ten of fifteen E1, E2, E3 and some of them were unnamed. We knew that we knew them but we didn’t know what they are. So we were simple minded elegant biochemists, not occupied with any idea and I think that in this competition he lost, I think, because he was …

He had a preconceived notion of what he was looking for.

Aaron Ciechanover: I think so. I mean he’s an excellent biochemist. He’s one of the fathers of the field, no doubt. But you know we’re coming to the subtleties of competition, it’s not competition of how we approached. And maybe he was preoccupied with the idea that there is only protease. Because just a few years before he finished purifying the longine product, the bacteria one, and the bacteria he was right. It’s an ATP-dependent protease that did the job. And he said let me find now the homolog of the bacterial system in the mammal cells and I think that that misled him.

Often that approach works but in this case not. So the discoveries you made were now obviously understood to be of immense importance. It’s an interesting question why it was almost a quarter of a century before you received the Lasker prize and then the Nobel Prize, given that there was fairly rapid recognition of the importance of the system.

Aaron Ciechanover: I can’t measure it on time scales or whether prize committees are waiting for it. But I think if I, let’s just go to the history of the ubiquitin system. I think that what happened is to our luck, actually I take it to our advantage. The first five, seven years were completely quiet, nobody still, despite all the papers that we poured, there were no other body working on the ubiquitin system. If you look into the literature under ubiquitin -83 you’ll find three papers. Who are the authors? Hershko and Ciechanover and Rose, doesn’t matter. And only in -84, Alex Varshavsky who was at MIT, then Alex Varshavsky slided in, he somehow appreciated it and we collaborated. Actually his first work with me, well he offered me a collaboration, he worked on some other aspect of ubiquitin genome, chromatim, but then we started to collaborate and then he took his own way and dissected the system very elegantly genetically, proving we were right biochemically. And then expanded it further, wonderful, elegant work.

But it was further expansion of the already known core route of knowledge of the system that was laid out in Israel before it came to America. So Alex was the first one to go in and then a few more people came in. But those people that came in were interested in degradation and this was still very slow. The real exponential deflection of the curve started only in the very late eighties, ten years after, and the early nineties. When people that worked on different proteins like P53 Peter Howley at the NAH, and Y. Mik or others, bumped in the system by chance – or Marc Kirschner at Harvard working on cyclins. And they found they had rapidly degrading proteins and then they started to ask themselves how these proteins are degraded, and they discovered that they are degraded by the ubiquitin system. So we saw kind of a revolution in the field that from ubiquitin people, we were ubiquitin people, and other few ubiquitin people like Cecile Pickart and Dan Finley at Harvard and others, all of a sudden the field became crowded with people that never were interested in degradation per se, but in their own substrate. And they decided, all of a sudden discovered that they belonged to the field. And then they acquired the tools and then it became exponential and then diseases and drugs.

The same 30, 40, 50 people kept on coming and we were the ubiquitin field …

In the mid-nineties it was clear that this is a block buster. So I would say that there are about seven, eight years of complete quietness between the late seventies and early and mid-eighties, whereh we were the only ones. Alex joined and then it started a little bit of deflection, more people joined until Martin Rechsteiner who discovered the protozone, Fred Goldberg at last was convinced that he was right and he came in. But again it was few. I mean I remember the first ubiquitin meetings, the facet meetings, were the same crowd. The same people kept on because there was no community. The same 30, 40, 50 people kept on coming and we were the ubiquitin field. And then Alex and then early eighties and late eighties and early nineties, and then thousands of people every year. I mean this was like a storm, a tsunami.

Was it nice to be in that period of almost a decade of working fairly much alone or did you actually want more input after a while? Did you hope that more people would join you?

Aaron Ciechanover: Retroactively I mean it was very nice. People told us you’ll lose your career but that’s minor. I mean you fail you do something again, maybe not important but unique, very nouvelle. So you don’t think of prizes, you don’t want to cure cancer, you think of what you do in the lab and it was nice. And it became complex and we discovered E1 and E2 and E3 and several histories and recognition of substrates. So we had a lot to do. So this was very interesting. I think that it’s very rare these days for such a system, I can compare it for example to SARNE which is a wonderful discovery and unbelievable. But it’s a system, it’s several enzymes that do what they do, /- – -/. We discovered I think, and again I don’t compare importance, don’t misunderstand me for a minute, I don’t say – there is nothing that is more or less important in biology, phosphorylation, but we discovered I think something, a huge iceberg. I mean that was still underneath.

And nobody could have predicted that this system, we discovered a system that has now almost 2,000 components, 1,500 components. It is involved everywhere and it’s not only in proteolysis. Ubiquitin like proteins say, routing of proteins to different subcellular destinations, to the nuclear por complex to the, from the cell membrane. And quality control, the whole quality control, /- – -/ the ubiquitin cell cycle and division, beautiful work of Tim Hunt, the cycle that goes up, it’s ubiquitin. I mean it’s only ubiquitin. Ubiquitin is everywhere and it’s not only for degradation. For me if I would have been asked a few years ago what’s ubiquitin, I would have said it’s a degradation signal. Now if somebody will ask me what’s ubiquitin I say it’s a passport. What’s a passport? Passport is a document that allows you to go to different countries. So if it ubiquitin certain way you go toward, you enter the country of the protozome. If ubiquitin another way you go to the world of the country of lysozome If ubiquitin /- – -/ you go to … it’s a very rich platform because you have several likes and many ubiquitin like proteins. So it’s very, it’s dynamic and it’s very flexible. You can use the same molecule to send different signals to different molecules to fulfil different functions.

So it’s first, now it’s extremely exciting to be there. I mean it’s, we are still competitive, we are doing very original work I believe in my lab. But it’s nice to know that you created a field, a humming field with 100,000 papers and laboratories and drug companies and thousands of researchers and conferences that you cannot even go any more. There are so many ubiquitin meetings, Cold Spring Harbour, Fasser, Embo, it’s endless, books, monographs, it’s a world of itself. But it’s rare, the fact that it was silent at the beginning basically let us lay down the entire system, not the system as we know it now, but the principles, conjugation, degradation … conjugation, recognition, degradation. And it’s an entirety. I mean we published 12 papers that are masterpieces that take you from A almost to Z. I mean the rest are as much as important as it is, genetics, the diseases, the drugs, are additional details that were added on it. But the core is in the paper. Now if people, you know, they’re RNA or let’s say reverse transcription, it’s an enzyme, that’s it. So it’s important but once you discover it that’s it, that’s the enzyme. Here it’s a huge thing that was hidden and I think that if people would have sensed that there is something important they would have jumped on it right there. So luckily they let us do it on our own and to really deploy and lay out the entire principles of the system, not the system. And that’s very nice.

… retroactively looking at it I think that we were extremely lucky that people were sceptical …

So I think that retroactively looking at it I think that we were extremely lucky that people were sceptical so that we are in the, either in the back yard of the back quarters of biology or even worse, having an artefact people also said, well that’s just an artefact. And I remember we sent the first paper to, not the first paper, the first conjugation paper to sell and there’d been /- – -/ round it and he said that he will consider publishing it if we will tell him what’s 1, 2, 3, 4, all the steps. 1,2 3 protozome /- – -/ And then Irwin Rose who was our co-/- – -/ sent it to PA, just communicated, and in a few days it was in. And people simply didn’t believe us. And that allowed us to really lay out the entire system which I believe will not happen today any more. I mean if people will sense that something is important they’ll jump on it. So it’s our time. As I told you, from ’78, basically from ’76, but our first paper came in ’78, the next important paper on ubiquitin system came only in ’84, I’m with Alex Varshavsky, the two, we had a back to back sell paper, some of the first ubiquitin. So this was the next one. So you can imagine six successive years of silence in the field. Can you imagine these days this will happen? No way, no, absolutely no way.

But another, now that just comes to my mind about the disbelief, came I think from Marc Kirschner, well he believed us from the very beginning. But that work on cyclins and degradation of cell cyclin, Avram also joined the field later. And Marc told me that he always saw the high molecular way junk at the top of the gel but he looked only into cyclin. And he thought that this high molecular way is the real junk, I mean it’s garbage. ‘Schmutz’ as he called it, it’s a ‘German schmutz’. And then he realised that this was ubiquitin cyclin and it’s gold basically, the ultimate gold. So it took him years to just get it. So I think the attitude obviously changed, but I think the people left us alone for a wonderful period of silence that I really cherish in retrospect.

Do you still teach your students that the series of 12 papers? Do you make them go back through it?

Aaron Ciechanover: Actually what we do when I teach advanced course, graduate course, the first two hours are reading plus my lecture about, not all the 12 of them, but the milestones among them. I think it is awfully important. And what I do more, which I’m going also tomorrow in my talk, I tell my students, and also tomorrow’s audience and every audience that I feel that I need to educate, that once you start a project it’s not you and me and I and me and I. What you do you look around you into the field and you see milestones. And then you try to connect them. You said what’s known now about proteolysis? Is the lysozyme /- – -/? What about energy? Who found that and who found that? Who cast now that it’s not the lysosome? And then you collect it.

… the beauty is the threads that leads from different milestones into a conclusion that ignites the process …

And there are many people to which we should pay tribute. I mean we were not isolated. You don’t start a problem by just, you’re not floating in a vacuum. There was Bob Shimkin, Rudolph Shemheimer and Fred Goldberg and others that laid the ground that convinced us, yes, there is something that is still hidden, let’s find it. So I think that the beauty is the threads that leads from different milestones into a conclusion that ignites the process. I mean you don’t ignite a process without having a car that has a gas tank, wheels, steering wheel, whatever. It all feeds into one, into the final pushing the button. And in our case or in the case of new discovery it’s a button that has never been pushed but never the less this button is always fed by whatever your predecessors put before you.

And I think that’s very important because students today, maybe even me, I don’t remember myself, thinks that science is being born with them and will die with them and they start something completely new. And I think that it’s awfully important, not only to give credit because it’s morally right, but to give credit as a lesson of how to approach science and how to build on past knowledge. It’s critically important and I do it repeatedly day in and day out, go to papers from 1935 and 1940, we take the JBC out and we just telling the history repeatedly. Because there is so much into it.

It’s hard work to explore the real history of such works.

Aaron Ciechanover: It’s worth every minute. Absolutely, it’s worth every minute.

And the ubiquitin system is in fact a particularly hard one to explore. There’s so many threads.

Aaron Ciechanover: It takes the students time, not only to explore it and to get into it, and obviously now we cannot follow it any more. There is no way that I can follow it. I follow a very narrow section of it from scription and /- – -/ because I follow a very narrow section of it. But I say to the students it takes them time to learn the language. So I call it, you know, I call the ubiquitin system, and I cool them down and they say Oh it’s so confusing, I don’t find my right leg from my left hand whatever. I said cool down, it’s like language, you know.

You start with, you know, it will take me, it will take you a year or two in the lab, and I direct them to some critical papers, reviews, to adapt, to learn the language. It’s a culture. I mean it’s like, you need to get into it. You know, the E1s and the E2s and the E3s and the /- – -/ the different chains and the protozome and the processes and the regulations. I mean it takes my students, despite the fact that they are in the ultimate ubiquitin lab, and we are doing biochemistry, I mean others are doing these genetics and so on, just to get into it. It’s a really long learning process. But I believe that it’s not unique to the ubiquitin system. I mean if you want to be a biologist that’s biology of today, that’s today’s biology. The genome, I mean the informatics, it’s …

You alluded to the fact earlier that your PhD experience made you approach your post doc in a particularly different way. What was it that you took from the Hershko experience?

And I started, we did beautiful work on it that is classic now …

Aaron Ciechanover: Well, when you go to a post doc and I remember coming to Harvey’s lab at MIT, and I consulted with Harvey. I wrote my post doc fellowship on something else. And then Harvey said, Harvey himself didn’t appreciate the ubiquitin system at that time and we are very good friends, and he said It’s very healthy that you’ll detach yourself from your past and start something new and then, from the ubiquitin whatever, do something else. Receptor /- – -/. And I started with it. It’s a matter of time. And I started, we did beautiful work on it that is classic now. It’s in Harvey’s text book of cell biology, cited a thousand times, on how the transferrin receptor releases iron into the cell transport – beautiful classic.

But then I became restless. I mean in a year into it, actually beforehand I became extremely restless and I said it must be stupid, I left behind such a beautiful system that is hardly the tip of the iceberg. I must go back. And luckily I had my own fellowship so I didn’t, you know, you feel more independent if somebody pays you out of his MIAge one. That’s one.

Second, Harvey is a terrific mentor. I mean he’s so liberal and so open and he’s not imposing. And he doesn’t care that people will do their own, I mean that’s very unique. And I said to him I want to go back to the ubiquitin system. He said Okay but keep a little bit on small fire what you did now because it’s so beautiful. All right, I flipped around day and night, whatever, weekends. And I went back to the ubiquitin system and then collaborated with Alex Varshavsky and he came with his ideas about, that was his entry to the field, and he came with wonderful ideas. But I worked on my own also. I published on my own as a post doc on the ubiquitin system, on the recognition motifs that later turned out to be part of the N-end rule that Alex worked but we needed biochemically, it doesn’t matter.

That is highly unusual.

Aaron Ciechanover: I was a freelancing post doc. I mean collaborating with another lab, work on my own, work on my, what my post doc mentor wants me to work on with receptor mediatedendocytosis. And basically it’s not only, you know, I was completely independent but there was also not much help around so I had to collaborate with Joan Steitz at Yale and even within MIT Harvey made me connected, he connected me to Uttam RajBhandary it doesn’t matter. I made my own connections and I collaborated at Harvard with /- – -/. So I was a very unusual – I think that it was a very unusual post doc fellowship. And it also laid the grounds for my independence because when I went back to Israel and started my own independent lab I was already independent.

I brought my subject from the post doctoral fellowship. I didn’t have to ask anybody. I didn’t have to ask Harvey can I take this project with me, it was my project. So I published I think four or five papers on the ubiquitin system on my own, collaborative with Aaron, when I was at MIT as a post doc. So it was just a restlessness that told me something is wrong, you left something too complex behind, how dare you? And that’s, it wasn’t wonderful. People don’t do it. Again I don’t take any credit, I don’t think that I’m courageous, I don’t think that I am exceptional.

But you know I think that there is something that I try to educated the young people I think and that’s, I tell them if you feel restless and you feel that this is not your place or you’re unhappy, don’t do it, change. When I felt restless I said that’s it, I must change, I will not do research /- – -/ to the end and that will be my future. I felt that I want to go back to ubiquitin, I stripped my bench from the remaining parts of receptor mediatedendocytosis and established my own system. I think that that’s the lesson mostly. Don’t do for forty years things that you are unhappy with. Just change. And I think that I wasn’t courageous, I just was myself. I did it in my military service, I did it everywhere. I never got stuck when I felt I shouldn’t get stuck.

But something that could be viewed as courageous was then after three years of post doc you moved back to Israel to Technion.

Aaron Ciechanover: Yes, I decided to go back to my country. It wasn’t that easy because I had offers in the United States in very good universities but I decided that culturally, historically, I wanted to go back. Avram also played an important role actively and passively. Actively by offering me a position in his department, independent position, we never worked together. Since I left the lab the only thing we did together was writing reviews to the Annual Review about chemistry.

We’re in the same building, same medical schools, same faculty, we never competed …

We never worked together and we don’t compete, we worked on completely different aspects. Still now. We’re in the same building, same medical schools, same faculty, we never competed. But also passively. Avram is a holocaust survivor and I said this country is not a usual country. I was born, I never suffered persecution or never was in Europe in the forties, I wasn’t born at the time. But I said I’m an officer in the Israeli army, that’s my country, that’s my language, these are my people, I want to go back. And if I can contribute by my own science now that I have big dreams, and I think that’s my place and it’s better than being in Stanford or whatever. And in retrospect I thought that it worked out very well, we were very successful.

But you were taking biology to what was essentially an engineering based university.

Aaron Ciechanover: Yes, and this was even harder because I had offers, even within Israel with more classical universities. But at that time Technion had started already a faculty of medicine and then there was a nucleus of a faculty of biology. And it was hard. Actually I must admit that my institute, with all due respect, because it’s number one university in Israel, I mean the entire engineering core of Israel rides on their shoulders. I mean there are very few institutes in the world that you can identify them with the very existence of a state, I mean success of a state. And my institute is clearly the one because the entire high tech industry of Israel, I mean whatever, computers, software, is riding on this institute. We poured out close to 100,000 engineers. I mean it’s a terrific engineering school.

But biology was not their strength and actually philosophically they were against it. They said we are strong, we have one of the ten best electric engineering departments in the world, computer sciences. Why do we need to dilute ourselves? And they never recognised the importance of biology and medicine even to engineering. Whatever I told them I brought MIT and I said look at MIT. I mean MIT is Massachusetts Institute not of biology, of technology. But never the less they had one of the best departments of biology in the world in the wider institute, Caltech. It’s California Institute of Technology and never the less they had an unbelievable department of biology. But now they’re okay. I think that it’s a wisdom retrospect because we were so successful and we brought them so much pride and fame. They recognised retroactively and now they pour a lot of money into life sciences and engineering and the interface between and now we are.

And now that the interface is more talked about and …

Aaron Ciechanover: And in retrospect now it turns out that we are the ideal place for doing it. There is no other university in Israel that can do it as good as we can because we have computer sciences, electric engineering, mathematics, physics, chemistry, all the engineering, biology, medicine, biomedical engineering. So now we are catching up and even, you know, starting to win the competition with others and to be the first again. But it took time. You see it’s, now I can look back and say how difficult it was and I say now the fight was worthwhile, never the less what brought them to think that that’s the way to go, let it be our fame or their own independent recognition that didn’t come on time. But it doesn’t matter. Now we are in the competition and in great shape. It’s a great institute altogether, it’s a great institute.

In general, how does Israeli science fare these days? What challenges does Israeli science face?

Aaron Ciechanover: I think that we are doing quite well. I mean we are a small country of six, seven million people with leading universities, the Weizmann Institute that you all know and you can point out to achievements. Let’s leave alone the ubiquitin system. Drug development, multiple sclerosis, Copaxon that came from the Weizmann Institute, Alzheimer drug, very successful and it came from. You can go not only to biology. You can go to the condensation of information that led later on to the development of the fax and computers and so on. It’s the Lempel-Ziv algorithm, something that was never patented but it came from the Technion. So Israel is very, you know we are exporting $20 billion a year of high tech. We don’t export oil, we are not Saudi Arabia, we don’t have one drop of our own oil. So all that we export.

… now we export knowledge. And it’s all a result of our educational system …

Initially we were a farm land, we exported oranges. And now we export knowledge. And it’s all a result of our educational system. The future I cannot tell you. I am a little bit more pessimistic. So to be realistic I am a little bit more pessimistic because the government cut some high education. Maybe they say we are successful and there are other needs and we are succumbing also to political settlements. Again I’m not expressing my opinion for or against but I say that different religious parties, I mean they are different sources, different channels to which the budget goes that should or shouldn’t go doesn’t matter, but never the less you are using budget for that. And the government is not that supportive as it should be in my opinion of high education. Also the very best scientists, we are still absorbed, we recruit the best scientists back. But some are already raising doubts whether they want to leave there because of the security, because of economy and so on and so forth. I think that we are doing good. We are okay now. I cannot predict for the future.

I mean there is a brain drain for different reasons, mostly, I don’t know if mostly, but security is clearly one of them. The instability in the area. Just a year ago we were bombarded with Hizbollah missiles. So I think that there is a place for concern about the future of science in Israel. But I think that learning and scholarly has always been a Jewish trait and in that sense I think I am not concerned, it will continue. Whether it will be in Israel I hope so and I will support it with all my power and spirit. I was born in this country and will die there, there is no doubt about it and will live the rest of my life in this place. Because for me it’s more than a country, it’s much more than a country and a place of living.

You must have entertained many, many offers to leave.

Aaron Ciechanover: Oh yes, all the time, numerous. But I will not do it. Maybe one year here or there but Israel will be my base for ever. But there is a place for concern and we do our best. It’s not simple place but never the less the past shows that we are doing very, very well. I mean the Hebrew University, Weizmann, Tel Aviv, Haifa, Basheba, the demand for education in Israel is huge and people just float there, you know, flock on the doors of universities. We cannot just absorb them all.

What a happy situation.

Aaron Ciechanover: It’s really amazing, it’s really amazing.

The Nobel Prize has many effects on many people, but what in particular has it done for you?

Aaron Ciechanover: Well, it had the same many effects like on many other people. It keeps me busy travelling all over the world. But I think that there is something that is, I don’t know if maybe unique to me, and the fact that I’m Jewish and Israel. And it opened the door for me to Jewish communities all over the world. And there are Jewish communities which are very diverse. I mean there are very rich Jewish communities and affluent and well to do in the United States. But on the other hand there are very small Jewish communities that you know cling to the walls and hardly survive, and never the less want to remain as they are. In Athens in Greece; Greece had half a million Jews, they were all exterminated in the holocaust. Now there are less than 5,000. Peru, 3,000. Paraguay, Ecuador, Uruguay. And there are two things about it that made me so excited about it. And the issue is extremely important to me.

… you blow an unbelievable wind in themselves, you fill them with pride …

As we talk Israel is my country, it’s not Israel as a nation, it’s the Jewish state, and the country was born after the holocaust in Europe because during the holocaust Jews were persecuted and murdered in Europe. So the timing of the establishment of the state of Israel is not just a random date. It’s a very particular date, ’47 and so on. And so the whole thing is very important for me. And I come to these Jewish – and I’ll tell you in a minute a story that is really important – I come to these Jewish communities and you see that you blow an unbelievable wind in themselves, you fill them with pride. There are many Jews who won Nobel Prizes, let’s don’t analyse numbers and reasons for it, it’s a unique phenomenon by itself. But an Israeli that speaks Hebrew, that’s served in the battle field, that was born in the year that the country was born, ’47, for them it’s something else.

And you see the cheerfulness, the joyfulness, the pride. I mean for me I feel like an ambassador of not only of my own country, without being an ambassador, and you see how important it is to them. And let me just end up with again one Jewish note. It was Saturday afternoon, I was invited to a meeting in Tomar, Portugal. It is a city 120 kilometres north-east of Lisbon. And I had to give a key note in a stress meeting, protein stress. It was the International Heat Check Society. And we drove from north of Spain we drove into Portugal, we arrived early and my son was with me. And we walked in the city, the city of Tomar, and we walked in the city and it’s a typically open city you know, the big square, the church, the city hall. And all of a sudden we see a small note saying synagogue, a small sign said synagogue. I said synagogue, let’s go and see the synagogue. So we start to crawl in back alleys and we get to the synagogue. And the synagogue is a very small room and nicely refurbished but completely erratic in its furniture. So you see that the chairs were brought from homes and on the walls there was some posters of El-Al which is Israel Airlines, with pictures of Jerusalem. But the walls were very nicely re-done.

And we looked around and we said yes and we read some sign about the history of the place. And the history was very interesting. It was established in 1430s and was closed sixty years later in the 1490s by a decree of King Emanuel I, the King of Portugal that married the daughter of Ferdinand and Isabel of Spain, and the condition for the marriage was obviously the enforcement of the inquisition laws in Portugal. And the Jews were forced to either leave the country or convert. And the synagogue was closed. And for 500 years it was offices, prison, whatever, belonged to the government. And in ’75, 1975, 500 years later it was re-opened once Salazar the dictator of Portugal was deposed and Portugal became democracy a few years after Spain. For 500 years these Jews that were converted became Iramos, they became crypted Jews, so they lived as Jews under the ground. To the eyes of the neighbours they were Christians. They went to the church, whatever. But at home in the most hidden way they kept a thin thread of Judaism.

So they didn’t keep it in full. They didn’t marry, they didn’t keep their Saturday, whatever, they just you know on Friday night they lighted the candles but they didn’t say any blessing. And it went from mother to daughter to son. I mean they never were told that they were Jews or anything. On Passover they did some residual ceremony and that’s it. No books, no nothing. And they kept their Judaism hidden. And all of a sudden in 1975 they floated up again and they became ultra-Orthodox Jews. Now the synagogue, we came to the synagogue and we read the history and they said it was closed because of this and that, and then we signed our name in the guest book. And the guy who was the guard of the synagogue saw that we were writing in Hebrew and we said We bless you for opening the synagogue. He said Are you from Israel? We said Yes we are from Israel. So all of a sudden we became … so he said to us I want to tell my story and his story is indeed the story.

He belonged to a Catholic family for 500 years, he grew up as Catholic, and in 1975 he’s 75 years old, all of a sudden he was converted to Judaism and became an ultra-Orthodox Jew. There are only two families in the city that were left, he and his friend, old friend, and they were appointed by the Portuguese government to guard the synagogue. And the Portuguese government takes very good care of them now because they want to revive Jewish life or at least the rich Jewish history. That’s just the beginning of the story but I’ll end it up with two very shortly and you’ll see how exciting and then you’ll understand why I’m so … So he said to me, You know it’s Saturday, why won’t you come tomorrow afternoon to the synagogue. I said You know Jews pray on Saturday, why should I come on Sunday? Sunday belongs as far as I can remember to the Christians, they go to church. He said, so he said to me There will be ceremony tomorrow afternoon, a ceremonial prayer in the synagogue. I said Ceremonial prayer in the synagogue, why on Sunday? He said You know tomorrow the first ever Israeli scientist that won a Nobel Prize is going to be our guest.

Wow! I said to him and I looked at my son and, you know, typically you come to these conferences and you are so busy, they load you with your schedule and you never look at it. And get up in the morning and my wife will say what shall we do? I said don’t worry, people will take us around, just don’t worry. We have a plan, let’s don’t worry about it. So it was on my schedule that I have to be in the synagogue for some ceremonial prayer and I didn’t look at it. So I look at my son and I said to the guy I suspect that you’re talking on me. And he couldn’t believe it. He just couldn’t believe it. And there was a silence in the room for a minute and then he fell on my shoulder with tears. And you know it was an unbelievable moment. We were the three of us alone in the synagogue, him, my son and myself, and for him it was the ultimate Jewish experience. I mean that here for the first time, you know, there are no Jews to pray there. You know they’re going to pray ceremonially celebrating the victory of science, whatever, with an Israeli Nobel Laureate and for him he was waiting for this ceremony. And all of a sudden somebody walks from the street, just at random, and we started to talk. So for him it was such an intimate moment. And me myself I broke in tears.

… this moment on Saturday afternoon I understood to the tiniest last smallest detail what I mean for these Jews …

And then the next day we came, the Israeli ambassador, I mean it was a very nice prayer, they kind of, Jews came, cryptic Jews came from all the villages around because the whole area was scattered with them, there was a huge Jewish community in Portugal at that time. And we celebrated but this moment on Saturday afternoon I understood to the tiniest last smallest detail what I mean for these Jews. I mean it’s unbelievable. And I said If I’m going ever to live in the state of Israel, it’s for him. So I mean that’s the Nobel Prize because without the Nobel Prize it would never have occurred, I would never have been invited. So the Nobel people don’t know about it at all what they did to my country, to me, to the Jewish community, it’s unbelievable experience.

It’s an enormous and joyous responsibility you have.

Aaron Ciechanover: Yes, I feel it by the way. I mean I don’t think, you know, I am an Israeli, I don’t know how many Israeli, we are very open, informal. Chutzpah, you know what’s chutzpah. Prudence. But I feel this responsibility. Not that I carry it you know under my bent shoulders but you do represent, it’s not only your country but the history of your people. For the last 2,000 years in some way. And when we talk there at the synagogue. And then I saw it in Uruguay and in Athens and Salonika and wherever I go you just see it. Obviously if you come to New York where three million Jews live, wealthy Jews and it’s nothing for them. But if you go to these tiny places, to Paraguay, to Ecuador, to Uruguay, to Buenos Aires, to Athens, to Hungary, different world. Just different world.

The embodiment of the success of the Jewish state.

Aaron Ciechanover: In a way and for them because they are so isolated. But the story of the cryptic Jews in Portugal is unbelievable, 500 years. I mean they could have mingled and mixed and didn’t care, but you know they kept it for 500 years and all of a sudden the torch came from underneath the table and they lighted it proudly, they didn’t care, and they said Yes, that’s it. And it’s just wonderful. For me it’s enlightening. I’m sorry that I imposed this story on you.

I’m not sorry at all.

Aaron Ciechanover: You asked me what the Nobel Prize did to me.

On the contrary, I’m not sorry you did at all. It was a fantastic story. I’m very glad to have heard it and I think other people will be too. Thank you very much indeed for sharing your thoughts.

Interview with the 2004 Nobel Laureate in Chemistry, Aaron Ciechanover, at the 57th Meeting of Nobel Laureates in Lindau, Germany, July 2007. The interviewer is Adam Smith, Editor-in-Chief of
Aaron Ciechanover talks about his mentors, the experiences that shaped his early interest in science (14:10), his research on the ubiquitin-mediated degradation system (21:40), the expansion of the field of ubiquitin research (31:06), and the personal significance of being an Israeli Nobel Laureate (57:28).

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